For most childhood cancers, aggressive medical treatments have led to 80 percent 5-year survival rates, resulting in more than 300,000 childhood cancer survivors in the United States. Although most of the adult survivors of childhood cancers (referred to as ACC-survivors) are cancer free, as many as 40 percent report troubling symptoms. Our long term goal is to generate novel and targeted interventions to reduce the impact of multiple burdensome symptoms on quality of life (QoL) outcomes for ACC-survivors. Using an innovative analytical approach for going beyond single symptoms, we propose to characterize unique subgroups of ACC-survivors using a five-symptom cluster of: pain, fatigue, sleep disturbance, psychological distress, and difficulty concentrating. In our preliminary study of 100 ACC-survivors, we found three distinct subgroup-specific symptom cluster experience profiles. Each subgroup also differed with respect to self-reported chronic health conditions and health-promoting lifestyle. Moreover, QoL varied significantly across subgroups, with lower QoL in the subgroup with the most intensive symptom cluster experience profile. As proposed in this study, further validation of these subgroups will strengthen the potential to identify ACC-survivors most in need of subgroup- specific targeted interventions. We propose to analyze data derived from 7147 ACC-survivors in the Childhood Cancer Survivor Study (CCSS), the world's largest multi-institutional long-term follow-up study of childhood cancer survivors. Using latent variable mixture modeling, we will empirically identify distinct symptom cluster experience profiles to define ACC-survivor subgroups. We will then test a set of risk and protective factors in relation to each of the subgroups. Finally, we will characterize the subgroups according to QoL variation as a means of indicating the extent of symptom cluster impact by subgroup and determine which subgroups have high needs for intervention. Strengths of this proposal by a well-rounded interdisciplinary research team include: 1) a focus on an evidence-supported five-symptom cluster in ACC-survivors, 2) cost-efficient use of data from a large high-quality database, and 3) implementation of innovative analytical methods for revealing distinct subgroup profiles, thus providing extraordinary potential to create novel, effective sub-group specific targeted interventions. PUBLIC HEALTH RELEVANCE: For most childhood cancers, aggressive medical treatments have led to 80 percent 5-year survival rates, resulting in more than 300,000 childhood cancer survivors in the United States. In this study we will identify subgroups of adult survivors of childhood cancers who have distinct patterns of troubling symptoms that interfere with quality of life. In the future, we will develop subgroup-specific strategies to relieve symptoms.